title: A Molecular Predictor Reassesses Classification of Human Grade II/III Gliomas.
abstract: Diffuse gliomas are incurable brain tumors divided in 3 WHO grades (II; III; IV) based on histological criteria. Grade II/III gliomas are clinically very heterogeneous and their prognosis somewhat unpredictable, preventing definition of appropriate treatment. On a cohort of 65 grade II/III glioma patients, a QPCR-based approach allowed selection of a biologically relevant gene list from which a gene signature significantly correlated to overall survival was extracted. This signature clustered the training cohort into two classes of low and high risk of progression and death, and similarly clustered two external independent test cohorts of 104 and 73 grade II/III patients. A 22-gene class predictor of the training clusters optimally distinguished poor from good prognosis patients (median survival of 13-20 months versus over 6 years) in the validation cohorts. This classification was stronger at predicting outcome than the WHO grade II/III classification (P≤2.8E-10 versus 0.018). When compared to other prognosis factors (histological subtype and genetic abnormalities) in a multivariate analysis, the 22-gene predictor remained significantly associated with overall survival. Early prediction of high risk patients (3% of WHO grade II), and low risk patients (29% of WHO grade III) in clinical routine will allow the development of more appropriate follow-up and treatments.
authors.affiliation: INSERM-UM1 U1040; CHRU Montpellier, Institute of Research in Biotherapy, Montpellier, France.
authors.forename: Thierry
authors.initials: T
authors.lastname: Rème
authors.forename: Jean-Philippe
authors.initials: JP
authors.lastname: Hugnot
authors.forename: Ivan
authors.initials: I
authors.lastname: Bièche
authors.forename: Valérie
authors.initials: V
authors.lastname: Rigau
authors.forename: Fanny
authors.initials: F
authors.lastname: Burel-Vandenbos
authors.forename: Vincent
authors.initials: V
authors.lastname: Prévot
authors.forename: Marc
authors.initials: M
authors.lastname: Baroncini
authors.forename: Denys
authors.initials: D
authors.lastname: Fontaine
authors.forename: Hugues
authors.initials: H
authors.lastname: Chevassus
authors.forename: Sophie
authors.initials: S
authors.lastname: Vacher
authors.forename: Rosette
authors.initials: R
authors.lastname: Lidereau
authors.forename: Hugues
authors.initials: H
authors.lastname: Duffau
authors.forename: Luc
authors.initials: L
authors.lastname: Bauchet
authors.forename: Dominique
authors.initials: D
authors.lastname: Joubert
mesh_terms: D000328:Adult; D001932:Brain Neoplasms / Q000145:classification / Q000235:genetics / Q000378:metabolism / Q000401:mortality; D016022:Case-Control Studies; D018572:Disease-Free Survival; D005260:Female; D020869:Gene Expression Profiling / Q000379:methods; D015972:Gene Expression Regulation, Neoplastic; D005910:Glioma / Q000145:classification / Q000235:genetics / Q000378:metabolism / Q000401:mortality; D006801:Humans; D008297:Male; D060787:Neoplasm Grading; D011237:Predictive Value of Tests; D015996:Survival Rate